There presently is no neuroprotective agent that can be given to patients with acute stroke. The costs for rehabilitation of patients that survive a stroke are greater than $40 billion per year in the U.S. The reason that an effective neuroprotective drug has not been developed so far, despite intensive efforts in the pharmaceutical industry, is that m most of the drugs do not cross the blood-brain barrier (BBB). Neurotrophins are potential large molecule neuroprotectives but these, too, do not cross the BBB. The present research plan aims at a merger of neurotrophin drug discovery and BBB drug targeting technology, so that a recombinant neurotrophin can be re-formulated to enable transport through the BBB in vivo. Such a drug will cause neuroprotection in stroke patients following intravenous administration. The goal of this work is to produce a genetically engineered fusion gene that encodes a fusion protein wherein the neurotrophin neuroprotective agent is fused to a genetically engineered chimeric monoclonal antibody (MAb) that undergoes receptor-mediated transport across the BBB in humans in vivo. The fusion protein will be a bi-functional molecule that not only crosses the BBB, but also binds to the target neurotrophin receptor in the brain in vivo. In phase I, the fusion gene will be produced and transiently. Transfected cell lines will be used to demonstrate the bi-functionality of the novel fusion protein. The bifunctionality of the fusion protein will be confirmed by immunoassay directed at both the BBB transporting receptor and the neurotrophin receptor. The phase 1_ work will produce a permanently transfected cell line secreting the fusion protein, and this protein will be manufactured and validated. At the completion of the phase II work, the company will be able to submit an IND to the FDA for testing of the new neuroprotective drug for stroke.